Summary Taste contributes to quality of life and healthy eating habits, aiding with the recognition of nutrients in food. The underlying molecular and cellular mechanisms responsible for transducing the taste of saccharides (sweet), amino acids (umami), and sodium (salty) have been characterized, but those responsible for detecting fat are controversial. Our preliminary studies indicate that an orphan G protein-coupled receptor, GPR113, is a bona fide fat taste receptor, and that the G? protein GNA14 transduces the fat taste signal from GPR113. Moreover, we have identified a subset of T1R+ taste cells expressing GPR113 and GNA14 that support fat taste. We propose to elucidate the roles of GPR113 and GNA14 in T1R+ taste cells. In Aim 1, we will record the behavioral and electrophysiological responses elicited by fat taste stimuli in Gpr113 knockout (KO) and Gna14 KO mice. In Aim 2, we will use a cell-based assay to deorphanize GPR113 and evaluate the contribution of GNA14 and T1Rs to the GPR113-dependent transduction pathway. In Aim 3, we will study the role of a transcription factor, FOXA2, that we hypothesize regulates the differentiation of fat taste cells. Knowledge obtained from this research will improve our understanding of the taste of fat and provide an opportunity to consider fat as a basic taste. As part of the project, we will establish a cell-based assay to screen for GPR113 modulators, which could potentially help develop fat taste enhancers that will allow us to reduce fat contents in our diets.